PMID- 30555566
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20200309
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 8
IP  - 20
DP  - 2018
TI  - miR-125a-5p ameliorates hepatic glycolipid metabolism disorder in type 2 diabetes 
      mellitus through targeting of STAT3.
PG  - 5593-5609
LID - 10.7150/thno.27425 [doi]
AB  - Glycolipid metabolic disorder is an important cause for the development of type 2 
      diabetes mellitus (T2DM). Clarification of the molecular mechanism of metabolic 
      disorder and exploration of drug targets are crucial for the treatment of T2DM. 
      Methods: We examined miR-125a-5p levels in palmitic acid-induced AML12 cells and 
      the livers of type 2 diabetic rats and mice, and then validated its target gene. 
      Through gain- and loss-of-function studies, the effects of miR-125a-5p via 
      targeting of STAT3 on regulating glycolipid metabolism were further illustrated 
      in vitro and in vivo. Results: We found that miR-125a-5p was significantly 
      decreased in the livers of diabetic mice and rats, and STAT3 was identified as 
      the target gene of miR-125a-5p. Overexpression of miR-125a-5p in C57BL/6 mice 
      decreased STAT3 level and downregulated the expression levels of p-STAT3 and 
      SOCS3. Consequently, SREBP-1c-mediated lipogenesis pathway was inhibited, and 
      PI3K/AKT pathway was activated. Moreover, silencing of miR-125a-5p significantly 
      increased the expression levels of STAT3, p-STAT3 and SOCS3, thus activating 
      SREBP-1c pathway and suppressing PI3K/AKT pathway. Therefore, hyperglycemia, 
      hyperlipidemia and decreased liver glycogen appeared in C57BL/6 mice. In palmitic 
      acid-induced AML12 cells, miR-125a-5p mimic markedly increased glucose 
      consumption and uptake and decreased the accumulation of lipid droplets by 
      regulating STAT3 signaling pathway. Consistently, miR-125a-5p overexpression 
      obviously inhibited STAT3 expression in diabetic KK-Ay mice, thereby decreasing 
      blood glucose and lipid levels, increasing hepatic glycogen content, and 
      decreasing accumulation of hepatic lipid droplets in diabetic mice. Furthermore, 
      inhibition of miR-125a-5p in KK-Ay mice aggravated glycolipid metabolism 
      dysfunction through regulating STAT3. Conclusions: Our results confirmed that 
      miR-125a-5p should be considered as a regulator of glycolipid metabolism in T2DM, 
      which can inhibit hepatic lipogenesis and gluconeogenesis and elevate glycogen 
      synthesis by targeting STAT3.
FAU - Xu, Lina
AU  - Xu L
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Li, Yue
AU  - Li Y
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Yin, Lianhong
AU  - Yin L
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Qi, Yan
AU  - Qi Y
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Sun, Huijun
AU  - Sun H
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Sun, Pengyuan
AU  - Sun P
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Xu, Ming
AU  - Xu M
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Tang, Zeyao
AU  - Tang Z
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Peng, Jinyong
AU  - Peng J
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181109
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Glycolipids)
RN  - 0 (MicroRNAs)
RN  - 0 (STAT3 Transcription Factor)
RN  - 2V16EO95H1 (Palmitic Acid)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Diabetes Mellitus, Type 2/*metabolism/therapy
MH  - Glucose Tolerance Test
MH  - Glycolipids/*metabolism
MH  - Lipid Metabolism/genetics/physiology
MH  - Lipogenesis/drug effects
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/genetics/*metabolism/*physiology
MH  - Palmitic Acid/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - STAT3 Transcription Factor/genetics/*metabolism
PMC - PMC6276304
OTO - NOTNLM
OT  - STAT3
OT  - metabolic disorder
OT  - miR-125a-5p
OT  - microRNA
OT  - type 2 diabetes mellitus
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2018/12/18 06:00
MHDA- 2019/09/10 06:00
PMCR- 2018/01/01
CRDT- 2018/12/18 06:00
PHST- 2018/05/23 00:00 [received]
PHST- 2018/10/12 00:00 [accepted]
PHST- 2018/12/18 06:00 [entrez]
PHST- 2018/12/18 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - thnov08p5593 [pii]
AID - 10.7150/thno.27425 [doi]
PST - epublish
SO  - Theranostics. 2018 Nov 9;8(20):5593-5609. doi: 10.7150/thno.27425. eCollection 
      2018.